Malignant melanoma is a major health problem in this country. Little is known regarding factors which contribute to the growth and progression of melanomas and early surgical removal is the only current effective treatment of this neoplasm. In recent years a number of cytokines have been identified as products of humans melanomas which may inhibit, promote, or have no effect on the growth of the melanoma. The broad long term objective of this proposal is to understand the biological significance and consequences of the secretion of specific cytokines by melanomas. The hypothesis to be tested in this proposal is the certain tumor-derived cytokines such as GM-CSF may play a key role in the pathogenesis of cutaneous melanoma. A murine model system to test this hypothesis was recently established. Preliminary studies indicate that GM-CSF can have a profound effect on the tumorigenicity of this neoplasm. The SPECIFIC AIMS of this application are; (I) To determine if there is genetic variability in the host response to GM-CSF producing melanomas, (II) To evaluate the consequences of melanoma GM-CSF production on tumor metastatic potential, (III) To evaluate the host immune response to GM-CSF producing murine melanomas, and (IV) To assess the therapeutic potential of GM-CSF for the treatment of established cutaneous melanomas. The results of this study could lead to novel diagnostic and therapeutic approaches in the management of malignant melanoma.